RSS-Feed abonnieren
DOI: 10.1055/s-0030-1263847
NAFLD patients exhibit dysregulation of bile acid transport in association with apoptosis and liver fibrosis
Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries and may proceed to steatohepatitis with and without fibrosis. However, the underlying pathophysiological mechanisms involved in fibrogenesis in NAFLD are scarcely understood. Recent data suggest elevation of bile acids in NAFLD. We aimed to characterize bile acid transporter expression as well as corresponding apoptosis and fibrosis in a cohort of NAFLD patients.
Methods: 49 morbidly obese patients who underwent bariatric surgery were included. Liver biopsies and serum samples were obtained during the procedure. Liver tissue was scored for NASH and investigated for intrahepatic expression of bile acid transporters as well as markers for apoptosis and fibrosis. The control group consisted of 10 healthy individuals.
Results: Expression-levels of the bile acid transporters NTCP (SLC10A1) and BSEP (ABCB11) were significantly upregulated in NAFLD patients. Further, the bile acid synthesizing enzyme CYP7A1 was dramatically overexpressed. In addition, expression of apoptosis related genes (NOXA, CD95/FAS, FASL) and serum M30 were increased. Further analysis revealed positive correlations between NTCP and NOXA. According to their M30 level, patients were grouped as NAFL (M30<275 U/ml) or NASH (>275 U/ml). Sirius Red stain demonstrated larger fibrotic tissue areas in NASH-Patients compared to the NAFL-group. We also found a positive correlation between NTCP and TGF-beta expression levels.
Conclusion: An increase of selected bile acid transporters strongly correlates with disease severity, markers of cell-death and especially fibrosis. Thus, understanding the role of bile acids and their cellular transporters in the pathogenesis of NAFLD might offer future therapeutic options for the most prevalent liver disease.